OBJECTIVE: Recent genome-wide association studies (GWAS) have identified multiple novel loci associated with adiposity in European-derived study populations. Limited study of these loci has been reported in African Americans. Here we examined the effects of these previously identified adiposity loci in African Americans. METHODS: A total of 46 representative single-nucleotide polymorphisms (SNPs) in 19 loci that were previously reported in GWAS in Europeans (including FTO and MC4R) were genotyped in 4992 subjects from six African-American cohorts. These SNPs were tested for association with body mass index (BMI) after adjustment for age, gender, disease status and population structure in each cohort. Meta-analysis was conducted to combine the results. RESULTS: Meta-analysis of 4992 subjects revealed seven SNPs near four loci, including NEGR1, TMEM18, SH2B1 /ATP2A1 and MC4R, showing significant association at 0.005<P<0.05, and had effect sizes between 0.04 and 0.06 s.d. units (or 0.30 to 0.44 g m(-2)) of BMI for each copy of the BMI-increasing allele. The most significantly associated SNPs (rs9424977, rs3101336 and rs2568958) are located in the NEGR1 gene (P=0.005, 0.020 and 0.019, respectively). CONCLUSION: We replicated the association of variants at four loci in six African-American cohorts that demonstrated a consistent direction of association with previous studies of adiposity in Europeans. These loci are all highly expressed in the brain, consistent with an important role for central nervous system processes in weight regulation. However, further comprehensive examination of these regions may be necessary to fine map and elucidate for possible genetic differences between these two populations.
OBJECTIVE: Recent genome-wide association studies (GWAS) have identified multiple novel loci associated with adiposity in European-derived study populations. Limited study of these loci has been reported in African Americans. Here we examined the effects of these previously identified adiposity loci in African Americans. METHODS: A total of 46 representative single-nucleotide polymorphisms (SNPs) in 19 loci that were previously reported in GWAS in Europeans (including FTO and MC4R) were genotyped in 4992 subjects from six African-American cohorts. These SNPs were tested for association with body mass index (BMI) after adjustment for age, gender, disease status and population structure in each cohort. Meta-analysis was conducted to combine the results. RESULTS: Meta-analysis of 4992 subjects revealed seven SNPs near four loci, including NEGR1, TMEM18, SH2B1 /ATP2A1 and MC4R, showing significant association at 0.005<P<0.05, and had effect sizes between 0.04 and 0.06 s.d. units (or 0.30 to 0.44 g m(-2)) of BMI for each copy of the BMI-increasing allele. The most significantly associated SNPs (rs9424977, rs3101336 and rs2568958) are located in the NEGR1 gene (P=0.005, 0.020 and 0.019, respectively). CONCLUSION: We replicated the association of variants at four loci in six African-American cohorts that demonstrated a consistent direction of association with previous studies of adiposity in Europeans. These loci are all highly expressed in the brain, consistent with an important role for central nervous system processes in weight regulation. However, further comprehensive examination of these regions may be necessary to fine map and elucidate for possible genetic differences between these two populations.
Authors: Sun J Kang; Charleston W K Chiang; Cameron D Palmer; Bamidele O Tayo; Guillaume Lettre; Johannah L Butler; Rachel Hackett; Adebowale A Adeyemo; Candace Guiducci; Ilze Berzins; Thutrang T Nguyen; Tao Feng; Amy Luke; Daniel Shriner; Kristin Ardlie; Charles Rotimi; Rainford Wilks; Terrence Forrester; Colin A McKenzie; Helen N Lyon; Richard S Cooper; Xiaofeng Zhu; Joel N Hirschhorn Journal: Hum Mol Genet Date: 2010-04-16 Impact factor: 6.150
Authors: Barry I Freedman; Pamela J Hicks; Meredith A Bostrom; Mary E Comeau; Jasmin Divers; Anthony J Bleyer; Jeffrey B Kopp; Cheryl A Winkler; George W Nelson; Carl D Langefeld; Donald W Bowden Journal: Nephrol Dial Transplant Date: 2009-06-30 Impact factor: 5.992
Authors: Maggie C Y Ng; Claudia H T Tam; Wing Yee So; Janice S K Ho; Alfred W Chan; Heung Man Lee; Ying Wang; Vincent K L Lam; Juliana C N Chan; Ronald C W Ma Journal: J Clin Endocrinol Metab Date: 2010-03-09 Impact factor: 5.958
Authors: Struan F A Grant; Jonathan P Bradfield; Haitao Zhang; Kai Wang; Cecilia E Kim; Kiran Annaiah; Erin Santa; Joseph T Glessner; Kelly Thomas; Maria Garris; Edward C Frackelton; F George Otieno; Julie L Shaner; Ryan M Smith; Marcin Imielinski; Rosetta M Chiavacci; Mingyao Li; Robert I Berkowitz; Hakon Hakonarson Journal: Obesity (Silver Spring) Date: 2009-03-05 Impact factor: 5.002
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Authors: Cecilia M Lindgren; Iris M Heid; Joshua C Randall; Claudia Lamina; Valgerdur Steinthorsdottir; Lu Qi; Elizabeth K Speliotes; Gudmar Thorleifsson; Cristen J Willer; Blanca M Herrera; Anne U Jackson; Noha Lim; Paul Scheet; Nicole Soranzo; Najaf Amin; Yurii S Aulchenko; John C Chambers; Alexander Drong; Jian'an Luan; Helen N Lyon; Fernando Rivadeneira; Serena Sanna; Nicholas J Timpson; M Carola Zillikens; Jing Hua Zhao; Peter Almgren; Stefania Bandinelli; Amanda J Bennett; Richard N Bergman; Lori L Bonnycastle; Suzannah J Bumpstead; Stephen J Chanock; Lynn Cherkas; Peter Chines; Lachlan Coin; Cyrus Cooper; Gabriel Crawford; Angela Doering; Anna Dominiczak; Alex S F Doney; Shah Ebrahim; Paul Elliott; Michael R Erdos; Karol Estrada; Luigi Ferrucci; Guido Fischer; Nita G Forouhi; Christian Gieger; Harald Grallert; Christopher J Groves; Scott Grundy; Candace Guiducci; David Hadley; Anders Hamsten; Aki S Havulinna; Albert Hofman; Rolf Holle; John W Holloway; Thomas Illig; Bo Isomaa; Leonie C Jacobs; Karen Jameson; Pekka Jousilahti; Fredrik Karpe; Johanna Kuusisto; Jaana Laitinen; G Mark Lathrop; Debbie A Lawlor; Massimo Mangino; Wendy L McArdle; Thomas Meitinger; Mario A Morken; Andrew P Morris; Patricia Munroe; Narisu Narisu; Anna Nordström; Peter Nordström; Ben A Oostra; Colin N A Palmer; Felicity Payne; John F Peden; Inga Prokopenko; Frida Renström; Aimo Ruokonen; Veikko Salomaa; Manjinder S Sandhu; Laura J Scott; Angelo Scuteri; Kaisa Silander; Kijoung Song; Xin Yuan; Heather M Stringham; Amy J Swift; Tiinamaija Tuomi; Manuela Uda; Peter Vollenweider; Gerard Waeber; Chris Wallace; G Bragi Walters; Michael N Weedon; Jacqueline C M Witteman; Cuilin Zhang; Weihua Zhang; Mark J Caulfield; Francis S Collins; George Davey Smith; Ian N M Day; Paul W Franks; Andrew T Hattersley; Frank B Hu; Marjo-Riitta Jarvelin; Augustine Kong; Jaspal S Kooner; Markku Laakso; Edward Lakatta; Vincent Mooser; Andrew D Morris; Leena Peltonen; Nilesh J Samani; Timothy D Spector; David P Strachan; Toshiko Tanaka; Jaakko Tuomilehto; André G Uitterlinden; Cornelia M van Duijn; Nicholas J Wareham; Dawn M Waterworth; Michael Boehnke; Panos Deloukas; Leif Groop; David J Hunter; Unnur Thorsteinsdottir; David Schlessinger; H-Erich Wichmann; Timothy M Frayling; Gonçalo R Abecasis; Joel N Hirschhorn; Ruth J F Loos; Kari Stefansson; Karen L Mohlke; Inês Barroso; Mark I McCarthy Journal: PLoS Genet Date: 2009-06-26 Impact factor: 5.917
Authors: Nancy L Heard-Costa; M Carola Zillikens; Keri L Monda; Asa Johansson; Tamara B Harris; Mao Fu; Talin Haritunians; Mary F Feitosa; Thor Aspelund; Gudny Eiriksdottir; Melissa Garcia; Lenore J Launer; Albert V Smith; Braxton D Mitchell; Patrick F McArdle; Alan R Shuldiner; Suzette J Bielinski; Eric Boerwinkle; Fred Brancati; Ellen W Demerath; James S Pankow; Alice M Arnold; Yii-Der Ida Chen; Nicole L Glazer; Barbara McKnight; Bruce M Psaty; Jerome I Rotter; Najaf Amin; Harry Campbell; Ulf Gyllensten; Cristian Pattaro; Peter P Pramstaller; Igor Rudan; Maksim Struchalin; Veronique Vitart; Xiaoyi Gao; Aldi Kraja; Michael A Province; Qunyuan Zhang; Larry D Atwood; Josée Dupuis; Joel N Hirschhorn; Cashell E Jaquish; Christopher J O'Donnell; Ramachandran S Vasan; Charles C White; Yurii S Aulchenko; Karol Estrada; Albert Hofman; Fernando Rivadeneira; André G Uitterlinden; Jacqueline C M Witteman; Ben A Oostra; Robert C Kaplan; Vilmundur Gudnason; Jeffrey R O'Connell; Ingrid B Borecki; Cornelia M van Duijn; L Adrienne Cupples; Caroline S Fox; Kari E North Journal: PLoS Genet Date: 2009-06-26 Impact factor: 5.917
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